Background: Lithium (LI) and clozapine (CLOZ) are the most evidence-based medications for preventing fatal and nonfatal suicidal behavior (SB). Unfortunately, both medications also can cause numerous medically serious side effects (SSEs). The VA is conducting a large randomized trial of LI for SB, and VA program offices are considering encouraging greater LI and CLOZ use. This study features a comprehensive database analysis and national survey to gather data to maximize the success of any effort to expand LI and CLOZ use. Specific Aims: 1) Rapidly Assess the Current Safety of LI & CLOZ & Identify Opportunities for Expanded Use; 2) Refine Knowledge about the Timing of SSE Risks and the Implications for Clinical Care; 3) Examine Use Across Providers & Identify Perceived Barriers / Facilitators to LI and CLOZ use; and 4) Integrate Results & Develop Policy Recommendations, Provider Guide, & Communication Tool. Significance: This study will markedly advance knowledge about how to safely use LI and CLOZ. These advances will include identifying the safest populations to target for expanded use, and how to best manage patients once LI and CLOZ are started. Understanding will be obtained about barriers besides SSEs that may impede wider LI and CLOZ use, and input will be obtained from providers on how to surmount these barriers. Findings will be integrated in several ways, including synthesis into a useful guide and communication tool. Priority Area(s): Suicide Prevention, Mental & Behavioral Health, and Predictive Analytics. Uniqueness: No prior study has examined the SSEs of LI or CLOZ as comprehensively, evaluated prevention and treatment strategies as thoroughly, or condensed its findings into tools for providers and patients. Methodology: Aim 1: Cox Regressions with Propensity Scores stratification will be used to facilitate the rapid estimation of risks associated in patient groups possessing plausible SSE risks factors (e.g., particular medical, psychiatric, or substance use diagnoses). Aim 2: Cox regression with marginal structural models will evaluate the emergence and development of risks over time, seeking to identify clinically-useful ?Decision Points?, and incidence rates will be derived to promote patient-provider communication regarding SSEs. Survey: A brief nationwide mental health prescriber survey focused on Barriers and Facilitators to Lithium use. Open response survey components will help ensure that any unanticipated barriers or facilitators to LI or CLOZ use will likely be identified. An all-cause mortality analysis and an example Predictive Model will help integrate results, as will an Advisory Board. A user-friendly Provider Guide and Patient-Provider Communication Tool will be developed. Expected Results: For LI and CLOZ, we expect to find some patient groups at lower risk than others for SSEs (e.g., male patients may be at lower risk for renal effects). We also expect immediate release LI to be associated with less renal risk. For CLOZ, we expect treatment of weight or metabolic risks at initiation to be beneficial. We also expect to find a ?trial window? during which risks of SSEs are fairly negligible, which may increase the willingness of patients to try LI or CLOZ. We expect the survey to find that SSEs are perceived as barriers to use, but also other barriers (e.g. a preference for medications without monitoring requirements). Next Steps: The study is expected to yield immediate policy recommendations (e.g., patient groups to target or not in any prescribing initiative) and valuable tools, since results are so directly transferable to patient care. Next steps might include immediate efforts by program offices to expand Li or CLOZ use. Alternatively, an implementation trial or staggered implementation could be initiated. Pilot testing of real-time risk calculators or qualitative studies of patient, provider or other key informant attitudes towards LI and CLOZ could also occur. Other Areas: This study will also support the safe use of these uniquely-valuable medications in non-suicidal patients. The survey findings will provide data that may inform future Provider Behavior interventions.